title: Iron and citrate export by a major facilitator superfamily pump regulates metabolism and stress resistance in Salmonella Typhimurium.
abstract: The efficacy of antibiotics and host defenses has been linked to the metabolic and redox states of bacteria. In this study we report that a stress-induced export pump belonging to the major facilitator superfamily effluxes citrate and iron from the enteric pathogen Salmonella Typhimurium to arrest growth and ameliorate the effects of antibiotics, hydrogen peroxide, and nitric oxide. The transporter, formerly known as MdtD, is now designated IceT (iron citrate efflux transporter). Iron efflux via an iron-chelating tricarboxylic acid cycle intermediate provides a direct link between aerobic metabolism and bacterial stress responses, representing a unique mechanism of resistance to host defenses and antimicrobial agents of diverse classes.
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Frawley
authors.forename: Marie-Laure V
authors.initials: ML
authors.lastname: Crouch
authors.forename: Lacey K
authors.initials: LK
authors.lastname: Bingham-Ramos
authors.forename: Hannah F
authors.initials: HF
authors.lastname: Robbins
authors.forename: Wenliang
authors.initials: W
authors.lastname: Wang
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Wright
authors.forename: Ferric C
authors.initials: FC
authors.lastname: Fang
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D019343:Citric Acid / Q000378:metabolism*; D019295:Computational Biology; D004251:DNA Transposable Elements / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D058085:Iron Compounds / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008857:Microscopy, Interference; D009569:Nitric Oxide; D018384:Oxidative Stress / Q000502:physiology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013308:Streptonigrin
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D058085:Iron Compounds; D026901:Membrane Transport Proteins; D013308:Streptonigrin; D019343:Citric Acid; D009569:Nitric Oxide
keywords: antibiotic resistance; oxidative stress